This invention relates to a process for preparing DL-serine, particularly to an industrial process for preparing DL-serine according to the Strecker reaction by use of glycol aldehyde as the reaction substrate. Further, this invention relates to a process for separation and purification of DL-serine, particularly to a process for separation and purification of DL-serine by subjecting the reaction mixture containing glycol aldehyde obtained by dehydrogenation or oxidative dehydrogenation of ethylene glycol to the Strecker reaction (Zelinsky-Stadnikoff reaction), recovering by separation of ethylene glycol from the mixture containig DL-serine obtained by hydrolysis of the reaction product obtained, and further separating inorganic salts therefrom.
Serine is an .alpha.-amino acid. L-serine is a compound useful as amino acid transfusion, and also D-serine is useful as a starting material for antibiotics. Also, serine is a compound useful as the starting material of L-tryptophan of which development is expected in an future as the additive for fodder.
As a method for synthesizing serine according to the Strecker reaction with glycol aldehyde as the reaction substrate, there has been already a report in Fischer and Leuchs: Chem. Ber., 35, 3787 (1902) that serine is obtained by use of alcoholic solution of ammonia, prussic acid and hydrochloric acid. The yield of serine by the method of said report is very low, and it is no more than confirmation of formation of serine.
As a process by use of a glycol aldehyde analogue as the starting material, Leuchs and Geiger: Chem. Ber., 39, 2644 (1906) and Dunn. Redemann and Smith: J. Biol. Chem., 104, 511 (1934) report preparation of serine by the Strecker reaction of ethoxy acetoaldehyde obtained by dehydrogenation of ethylene glycol monoethyl ether, hydrolysis with hydrogen bromide and cleavage of ethyl group, but also the yield is low and the starting material is expensive, involving also the problems such as corrosion of the reaction vessel, etc. Thus, it can hardly be said to be a production process industrially practiced.
Also, Japanese Patent Publication No. 11309/1982 discloses a process for preparing serine by use of a glycol aldehyde precursor such as monochloroethylene oxide, etc. The yield by the process in said Publication is about 50 %, and synthesis of the starting material is also cumbersome and this process is not satisfactory as production process industrially practiced.
Also, for glycol aldehyde which is the starting material for preparation of serine, there has not yet been established an industrial production process, particularly because it cannot be easily isolated and purified. Thus, the process for preparing serine according to the Strecker reaction with the use of glycol aldehyde or its related substance as the starting material is only disclosed in several literatures including the above-mentioned report.
In none of the preparation methods, detailed investigation has been done about the Strecker reaction in which various reaction factors participate, and they involve problems as production processes industrially practiced.
As described above, preparation of serine from glycol aldehyde or its analogue has been known for long time, as reported in Fisher & Leuchs, Chem. Ber., 35, 3787 (1902), Japanese Patent Publication No. 11309/1982, etc., but its examples are few, and no industrial production process has been established. This is because preparation method of glycol aldehyde itself has not yet been established. Particularly, isolation and purification of glycol aldehyde are difficult because alcohol aldehyde has such physical properties that it is soluble in water, and also high in reactivity to be thermally unstable.
As a method for separating and purifying the synthesized serine, there is the method for preparing DL-serine from glycol aldehyde triacetate in which .alpha.-amino-.beta.hydroxypropionitrile is prepared according to the Strecker reaction, and this is hydrolyzed with hydrochloric acid [Chem. Ber., 98, 1677 (1965)], and according to this method, after concentration of the hydrochloric acid hydrolyzed mixture to dryness, the DL-serine hydrochloride is extracted with ethanol, which is then neutralized with diethylamine or ammonia. However, concentration to dryness is industrially feasible with difficulty, and entrainment of impurities of inorganic salts, etc. may be conceivable, and also DL-serine crystallized by neutralization also contains a viscous polymer, whereby filtrability is poor and also the DL-serine purity is low.
There has been also proposed a method in which .alpha.-amino-.beta.-hydroxypropionitrile is hydrolyzed with the use of 7-fold moles or less of sodium hydroxide, and the DL-serine formed is adsorbed onto an acidic ion exchange resin (Japanese Patent Publication No. 3325/1969). However, according to this method, during adsorption of DL-serine onto the acidic ion exchange resin, a great excess of coexisting sodium ions are also adsorbed at the same time, and therefore an extremely large amount of the ion exchange resin is required and also a large amount of aqueous ammonia is also used for desorption. Thus, it cannot be said to be an economical method.
Also, in Japanese Patent Publication No. 48528/1974, there is proposed a method in which a DL-serine hydrochloride-containing solution containing an acid is concentrated, the acid is evaporated with a large excess amount of water, and thereafter the water is replaced with a large excess amount of methanol or ethanol, inorganic salts are filtered, and alcohol is recovered, and then serine is adsorbed onto an acidic ion exchange resin, followed by elution with ammonia water. However, since this method uses large amounts of water and alcohol, and also the separation and purification steps are lengthy, it can be far from industrial process.
Thus, all of the separation and purification methods of synthesized serine known in the art are cumbersome in operations and also use a large amount of aids to be little practically available as industrial separation and purification process.
On the other hand, concerning separation and purification of amino acids by use of ion exclusion chromatography, Japanese Unexamined Patent Publication No. 255452/1987 discloses an example in which the aqueous isoleucine solution prepared by the fermentation method is applied as such. However, no good result can be obtained if the above method may be applied as such to the crude aqueous serine solution in which serine salt and ionic substances such as inorganic salts, etc. and substances having no ionic characteristic such as ethylene glycol, etc. coexist.